In vitro assessment of the impact of di(2-ethylhexyl) phthalate and its metabolites on the function and transcription of key glucose sensing proteins in a rat pancreatic β-cell line

OBJECTIVE: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in everyday products, making human exposure unavoidable. DEHP exposure has been associated with disruptions in insulin secretion. This study assessed the in vitro effects of DEHP and its metabolites, mono(2-ethylhexyl) phthalate (MEHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), on the function and transcription of glucose transporter 2 (GLUT2) and glucokinase in RIN-5 F pancreatic β-cells. Cells were exposed to various chemical concentrations; glucose uptake, glucokinase activity and gene expression were assessed. RESULTS: Short-term exposure to DEHP and MEHP disrupted glucose uptake at normal glucose, however, the effects were not evident at high glucose or following the 24-hour exposure period. Glucokinase activity was not significantly altered by the treatments. Preliminary gene expression analysis after 24-hour chemical exposure indicated upregulation of GLUT2 transcription while MEHP additionally enhanced glucokinase gene expression, without corresponding alterations at a functional level. The findings suggest that DEHP and its metabolites modulate the function and transcription of key proteins in the pancreatic β-cells glucose sensing system. This highlights the importance of assessing DEHP exposure effects on processes upstream of insulin secretion in β-cells. The study provides a basis for future investigations incorporating quantitative PCR, protein expression and GLUT2 localization to validate these findings.